Receptor ACE2—A Key Target for Novel Coronavirus Infections

An ongoing outbreak of a novel coronavirus (SARS-CoV-2) has raised global concerns. It is identified as the cause of pneumonia with unknown etiology. Since the early outbreak in Wuhan, China, it has subsequently spread to all provinces of China and many other countries. In fact, coronavirus is a relatively common human virus, which causes 10% of the common colds. However, some coronaviruses are more harmful, such as SARS-CoV and MERS- CoV and the novel coronavirus, named SARS-CoV-2.

How does SARS-CoV-2 infect patients?

Spike protein (including S1 and S2 subunits) is the most important pathogenic protein of coronavirus, which helps the virus to bind to the transmembrane receptor protein on the human cell membrane, thereby helping itself to enter the cell.

The latest research shows that the Spike proteins of SARS-CoV-2 and SARS-CoV are more conserved, and in vitro experiments have proved that as long as the cell expresses ACE2, SARS-CoV-2 can infect cells; on the contrary, if there is no ACE2 on the cell protein, it will not be infected. Therefore, it is believed that SARS-CoV-2 is mediated into the interior of cells through the binding of Spike proteins to ACE2 proteins, which may become a breakthrough in the study of SARS-CoV-2.

What is ACE2 protein?

The ACE2 gene is located on the X chromosome, which encodes a type I transmembrane glycoprotein with a single extracellular catalytic domain. ACE2 has a well-known homologous gene, ACE, which is also an angiotensin-converting enzyme. ACE and ACE2 both have two domains: the amino-terminal catalytic domain and the carboxy-terminal domain).

Despite similarities, ACE2 and ACE function differently. ACE's role is to convert angiotensin I (AngI) to active angiotensin II (AngII), thereby increasing hypertension. The role of ACE2 is to convert AngII to heptapeptide angiotensin 1-7 (Ang1-7), and then antagonize the blood pressure-increasing effect of AngII, which has a negative regulatory effect on the RAS system. Therefore, ACE2 functions completely differently from ACE and the two work together to balance blood pressure.

Lessons from SARS

Due to the function of ACE2, previous basic clinical studies have linked it with hypertension and cardiovascular disease, but in 2003, after ACE2 was identified as an essential receptor for SARS coronavirus infection, its research in this area has been carried out. And because the pathogenic mechanism of SARS-CoV-2 is highly similar to SARS of 2003, the current research of SARS is extremely informative.

In 2003, researchers identified ACE2 as a functional SARS-CoV receptor by co-immunoprecipitation technology. Subsequently, ACE2 was identified as an essential receptor for SARS infection in vivo in the ACE2-knockout mouse model. However, previous studies have found that ACE2-knockout mice with lung injury have a more severe acute injury and higher mortality than the wild-type mice, suggesting that ACE2 deficiency may worsen the symptoms of acute lung injury. Therefore, ACE2-mediated degradation of AngII is important for lung protection against the pathogenesis of pneumonia causing by SARS-CoV infection.

To unveil the secret of SARS-CoV-2, more research is needed, and at the same time, scientists worldwide are dedicated to finding methods of more accurate diagnosis and more efficient treatment.